In 1993, Malawi was the first country to switch from choloroquine to sulfadoxine-pyrimethamine (SP) as first line anti-malarial therapy due to unacceptably high failure rates with chloroquine. Studies of SP efficacy in Malawi from 1998 to 2002 have documented approximately 80% therapeutic efficacy at 14 days, with a modest increase in parasitological resistance and 28 day therapeutic efficacy. These results attest to the durability of SP efficacy, but also warn that increasing failure rates are likely to occur in the future. Following the unexpected finding that chloroquine efficacy has re-emerged after discontinuing its use 10 years ago, the candidate's mentor, Dr. Christopher Plowe, will conduct a longitudinal trial to assess the clinical and parasitological efficacy of chloroquine monotherapy and chloroquine in combination with other drugs as compared to SP alone, the current standard of care. The candidate will be completing her fellowship in pediatric infectious diseases and has been working with Dr. Plowe in Malawi. She will conduct a molecular evaluation of the parasites isolated from the participants in this clinical trial to look for the single nucleotide polymorphisms associate with chloroquine and SP resistance. These data will be analyzed to assess the ability of combination therapy to protect against the emergence of resistance-conferring mutations in comparison to monotherapy. In addition, she will test the hypothesis that there is a stable relationship between prevalence rates of resistant mutations and in vivo resistance over time in order to validate a model that uses molecular markers for drug resistant malaria as a surveillance method to monitor changes in drug efficacy. The candidate's career development plan is to gain the skills necessary to conduct clinical trials and analyze complex epidemiological data. She will be mentored by Dr. Plowe at the Center for Vaccine Development at the University of Maryland and Dr. Terrie Taylor at the Blantyre Malaria Project in Malawi, and will complete a Master's degree in Public Health. The candidate's long-term career goals are to become an independent investigator in an academic setting and to conduct clinical and epidemiological research that applies molecular techniques to address public health problems in developing countries.